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Investigation of local immune responses at the maternal-fetal interface during infection with Porcine Reproductive and Respiratory Syndrome Virus
Andrea Ladinig
Wilhelm Gerner
PhD thesis - University of Veterinary Medicine Vienna - 2023
In humans and mice, extensive research on the phenotype and function of immune cells that reside at the maternal-fetal interface has been performed with the goal to understand the complexity of reproductive immunology. In pigs, however, studies that addressed immune cell phenotypes at the maternal-fetal interface mainly focused on early gestation, whereas late gestation has not been investigated so far. In addition, the literature available so far only addressed the major lymphocyte subsets without going into much detail. Therefore, this PhD thesis aimed to establish a methodology tailored to porcine epitheliochorial placenta which would allow for the investigation of the immune cell composition in the maternal endometrium (ME) and fetal placenta (FP) separately. In the first study we performed in-depth phenotyping experiments for the characterization of natural killer cells (NK), non-conventional, and conventional T cells within maternal blood (mBld), ME, FP, and fetal spleen (fSpln). The results showed that between the investigated anatomic locations that observed NK and T cell phenotypes were considerably different. Lymphocyte subsets originating from the maternal compartments (mBld and ME) displayed highly differentiated phenotypes. Furthermore, even in the absence of any stimuli, lymphocytes isolated from the maternal compartments had a high capacity to spontaneously release interferon-gamma (IFN-γ) which reflected the high degree of NK and T cell differentiation within those anatomic sites. In the fetal compartments (FP and fSpln), mainly naive phenotypes were found. Nevertheless, also differentiated phenotypes e.g. CD2+CD8α+CD27dim/-perforin+ γδ T cells, CD27-perforin+ cytolytic T cells (CTLs), and T-bet+CD4+CD8α+CD27- Tem cells were identified in the FP. Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure during late gestation. As to date, the local immune response at the maternal-fetal interface remains poorly characterized and specific literature available is sparse. Therefore, our second study aimed to investigate the phenotypic changes at the maternal-fetal interface following PRRSV infection and/or vaccination in a reproductive gilt model. A total of twenty-four gilts were included, twelve gilts were vaccinated with a modified live virus (MLV) vaccine whilst the other twelve gilts were not. During late gestation (day 84) gilts were challenged with either one of the two selected PRRSV-1 field isolates or sham-inoculated with cell culture medium. Three weeks postinfection all gilts and their litters were euthanized and two fetuses per gilt were randomly selected in order to study the local immune response in the ME and FP. In non-vaccinated gilts, infection resulted in a strong expansion of effector lymphocytes which might contribute to pathology at the maternal-fetal interface rather than confer protection. A more contained immune response was observed in the vaccinated gilts and conferred protection. Taken together, these studies provide the groundwork to further explore local immunity in utero and provide insight into local events in response to PRRSV infection. Furthermore, the same methodology could be applied to other pathogens that cause reproductive failure.
Englisch
2023
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